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Corticosteroids reduce symptoms of croup in children within two hours and continue to do so for at least 24 hours. They also cut the amount of time children spend in hospital by 15 hours and reduce return visits or readmissions from about 20% to 10%.

This Cochrane review assessed the effectiveness of corticosteroids such as dexamethasone and budesonide compared with placebo. It updates a previous review which concluded that corticosteroids reduce symptoms of croup at six hours.

The review also found that dexamethasone is more effective than budesonide at reducing croup symptoms at 6 and 12 hours - and lessens the need for adrenaline. However, rates of return visits and/or readmissions were similar, and there was no additional benefit from combining the two drugs.

The findings support recommendations that all children with mild, moderate, or severe croup should be treated immediately with corticosteroids.

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Why was this study needed?

Croup, or laryngotracheobronchitis, is a common childhood respiratory condition, characterised by the sudden onset of a seal-like barking cough, often accompanied by high-pitched wheezing, a hoarse voice, and difficulty breathing. It affects around 3% of children per year - mostly between the ages of six months and three years - and is caused by swelling in the larynx and trachea triggered by a recent viral infection.

Although it has long been recognised that corticosteroids provide some clinical benefit for children with croup, many children don’t receive them, and there is continued medical debate in the timing of their use in this context.

The current review is an update of a Cochrane Systematic Review that was first published in 1999 and updated in 2004 and 2011. It incorporates five newly published studies and is the first time that risk of bias in the included studies, and the certainty of the evidence, have been assessed with the respective Cochrane tools.

What did this study do?

The review compared the effectiveness of corticosteroids to placebo for treating croup in children. It assessed whether they reduced croup symptoms, minimised return visits or shortened length of hospital stay, reduced the need for additional treatments, or had side effects.

The 43 studies (including five new to this update) covered 4,565 children. The corticosteroids investigated included beclomethasone, betamethasone, budesonide, dexamethasone, fluticasone, and prednisolone. Most studies compared corticosteroids to placebo, although some compared them to adrenaline, to another corticosteroid, or combination of corticosteroids; or compared corticosteroids given in different ways, or amounts.

The studies took place in North America, Europe, Asia and Australia.

Few studies had a low overall risk of bias, and many biases were unclear from the reporting. However, using the GRADE system the certainty of evidence was thought to be moderate meaning that readers can be moderately confident in the effect estimate.

The rates of return visits or (re)admissions or both were halved by corticosteroids (risk ratio 0.52, 95% CI 0.36 to 0.75). When given corticosteroids, 106 of every 1,000 children treated will return for medical care, compared with 204 of every 1,000 children treated with placebo.

Corticosteroids reduced children’s length of hospital stay by 15 hours (range 6 to 24 hours) compared with placebo, but made no difference to their need for additional treatments.

Few serious adverse events were associated with short‐term corticosteroid treatment for croup.

What does current guidance say on this issue?

The NICE Clinical Knowledge Summary on croup (updated in 2017) recommends that all children with mild, moderate, or severe croup should receive a single dose of oral dexamethasone (0.15 mg per kg body weight). If the child is too unwell to receive medication, inhaled budesonide (2 mg nebulised as a single dose) or intramuscular dexamethasone (0.6 mg/kg as a single dose) are alternatives.

What are the implications?

The findings of this large, high quality review reinforce current recommendations and practice with a moderate degree of certainty. They suggest that corticosteroids rapidly reduce symptoms of croup in children, within about 2 hours and that the effect lasts for at least 24 hours.

The findings may support earlier escalation of therapy (following a lack of response at 2 hours).

Shorter hospital stays and the reduction in readmission rates from about 20% to 10% are important outcomes for health systems and commissioners of child services.

Why was this study needed?

Croup, or laryngotracheobronchitis, is a common childhood respiratory condition, characterised by the sudden onset of a seal-like barking cough, often accompanied by high-pitched wheezing, a hoarse voice, and difficulty breathing. It affects around 3% of children per year - mostly between the ages of six months and three years - and is caused by swelling in the larynx and trachea triggered by a recent viral infection.

Although it has long been recognised that corticosteroids provide some clinical benefit for children with croup, many children don’t receive them, and there is continued medical debate in the timing of their use in this context.

The current review is an update of a Cochrane Systematic Review that was first published in 1999 and updated in 2004 and 2011. It incorporates five newly published studies and is the first time that risk of bias in the included studies, and the certainty of the evidence, have been assessed with the respective Cochrane tools.

What did this study do?

The review compared the effectiveness of corticosteroids to placebo for treating croup in children. It assessed whether they reduced croup symptoms, minimised return visits or shortened length of hospital stay, reduced the need for additional treatments, or had side effects.

The 43 studies (including five new to this update) covered 4,565 children. The corticosteroids investigated included beclomethasone, betamethasone, budesonide, dexamethasone, fluticasone, and prednisolone. Most studies compared corticosteroids to placebo, although some compared them to adrenaline, to another corticosteroid, or combination of corticosteroids; or compared corticosteroids given in different ways, or amounts.

The studies took place in North America, Europe, Asia and Australia.

Few studies had a low overall risk of bias, and many biases were unclear from the reporting. However, using the GRADE system the certainty of evidence was thought to be moderate meaning that readers can be moderately confident in the effect estimate.

The rates of return visits or (re)admissions or both were halved by corticosteroids (risk ratio 0.52, 95% CI 0.36 to 0.75). When given corticosteroids, 106 of every 1,000 children treated will return for medical care, compared with 204 of every 1,000 children treated with placebo.

Corticosteroids reduced children’s length of hospital stay by 15 hours (range 6 to 24 hours) compared with placebo, but made no difference to their need for additional treatments.

Few serious adverse events were associated with short‐term corticosteroid treatment for croup.

What does current guidance say on this issue?

The NICE Clinical Knowledge Summary on croup (updated in 2017) recommends that all children with mild, moderate, or severe croup should receive a single dose of oral dexamethasone (0.15 mg per kg body weight). If the child is too unwell to receive medication, inhaled budesonide (2 mg nebulised as a single dose) or intramuscular dexamethasone (0.6 mg/kg as a single dose) are alternatives.

What are the implications?

The findings of this large, high quality review reinforce current recommendations and practice with a moderate degree of certainty. They suggest that corticosteroids rapidly reduce symptoms of croup in children, within about 2 hours and that the effect lasts for at least 24 hours.

The findings may support earlier escalation of therapy (following a lack of response at 2 hours).

Shorter hospital stays and the reduction in readmission rates from about 20% to 10% are important outcomes for health systems and commissioners of child services.

Glucocorticoids for croup in children

BACKGROUND: Glucocorticoids are commonly used for croup in children. This is an update of a Cochrane Review published in 1999 and previously updated in 2004 and 2011.
OBJECTIVES: To examine the effects of glucocorticoids for the treatment of croup in children aged 0 to 18 years.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 2, 2018), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE (1946 to 3 April 2018), and Embase (Ovid) (1996 to 3 April 2018, week 14), and the trials registers ClinicalTrials.gov (3 April 2018) and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 3 April 2018). We scanned the reference lists of relevant systematic reviews and of the included studies.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated children aged 0 to 18 years with croup and measured the effects of glucocorticoids, alone or in combination, compared to placebo or another pharmacologic treatment. The studies needed to report at least one of our primary or secondary outcomes: change in croup score; return visits, (re)admissions or both; length of stay; patient improvement; use of additional treatments; and adverse events.
DATA COLLECTION AND ANALYSIS: One author extracted data from each study and another verified the extraction. We entered the data into Review Manager 5 for meta-analysis. Two review authors independently assessed risk of bias for each study using the Cochrane 'Risk of bias' tool and the certainty of the body of evidence for the primary outcomes using the GRADE approach.
MAIN RESULTS: We added five new RCTs with 330 children. This review now includes 43 RCTs with a total of 4565 children. We assessed most (98%) studies as at high or unclear risk of bias. Compared to placebo, glucocorticoids improved symptoms of croup at two hours (standardised mean difference (SMD) -0.65, 95% confidence interval (CI) -1.13 to -0.18; 7 RCTs; 426 children; moderate-certainty evidence), and the effect lasted for at least 24 hours (SMD -0.86, 95% CI -1.40 to -0.31; 8 RCTs; 351 children; low-certainty evidence). Compared to placebo, glucocorticoids reduced the rate of return visits or (re)admissions or both (risk ratio 0.52, 95% CI 0.36 to 0.75; 10 RCTs; 1679 children; moderate-certainty evidence). Glucocorticoid treatment reduced the length of stay in hospital by about 15 hours (mean difference -14.90, 95% CI -23.58 to -6.22; 8 RCTs; 476 children). Serious adverse events were infrequent. Publication bias was not evident. Uncertainty remains with regard to the optimal type, dose, and mode of administration of glucocorticoids for reducing croup symptoms in children. AUTHORS' CONCLUSIONS: Glucocorticoids reduced symptoms of croup at two hours, shortened hospital stays, and reduced the rate of return visits to care. Our conclusions have changed, as the previous version of this review reported that glucocorticoids reduced symptoms of croup within six hours.

Expert commentary

This update has introduced new methodology to reduce possible study bias and thus strengthen the certainty of their findings.

The new conclusion (since the 2011 review) that symptom improvement can be seen as quickly as two hours (rather than six hours) will not change the clinical practice of using nebulised or oral corticosteroids for infants with significant croup. However, perhaps now a lack of response by two hours may be a signal to offer additional therapy.

Expert commentary

If you were in any doubt - corticosteroids are helpful in croup. The benefit at two hours identified in this review helps put to bed the four hour lag suggested by some for an initial steroid response.

Early use of a single dose even in milder croup should be prescribed at the earliest opportunity. Hopefully, in time, we will better understand which children are at highest risk of rebound after an initial dose.

Steve Cunningham, Professor of Paediatric Respiratory Medicine, University of Edinburgh